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Reactive Oxygen Species Mediate Angiotensin‐II (Ang‐II)‐Dependent Activation of Calcium/Calmodulin Dependent Kinase II (CaMKII) in Forebrain Circumventricular Organs (CVOs)
Author(s) -
Peterson Jeffrey,
Stupinski John A.,
Sharma Ram V.,
Davisson Robin L.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.741.3
Subject(s) - angiotensin ii , lamina terminalis , chemistry , medicine , endocrinology , forebrain , reactive oxygen species , receptor , microbiology and biotechnology , biology , central nervous system , biochemistry
Reactive oxygen species (ROS) play a crucial role in central Ang‐II signaling. However, the downstream effectors of Ang‐II‐induced ROS in neurons are not known. Here, we tested the hypothesis that Ang‐II‐dependent activation of CaMKII in CVOs is redox‐sensitive. First, Neuro‐2A cells were treated with adenovirus expressing CuZnSOD (AdCuZnSOD), a control vector (AdLacZ), or vehicle for 24 hrs and stimulated with Ang‐II (1μM, 30 min). CaMKII activation was measured by immunofluorescence using an antibody against the autophosphorylated form (pCamKII). Ang‐II induced a marked increase in pCaMKII levels in control cells which was significantly inhibited by treatment with AdCuZnSOD (saline 1.5±.02, AdLacZ 1.7±.06 vs AdCuZnSOD 1.2±.04 fold vs baseline, p<.05, n=27–61 cells). We next examined the role of ROS in CaMKII activation in forebrain CVOs during slow‐pressor Ang‐II infusion. Following forebrain CVO‐targeted delivery of AdCuZnSOD or AdLacZ, mice underwent either saline or slow‐pressor Ang‐II infusion. CaMKII activation was assessed by western analysis for pCaMKII in pooled (n=3) micropunches from the lamina terminalis taken at day 16 during the infusions. In AdLacZ‐treated mice, Ang‐II induced a significant (1.7±.02 fold) increase in CaMKII activation in forebrain CVOs as compared to saline. Importantly, treatment with AdCuZnSOD blunted this rise in activated CaMKII (1.1±.04 fold increase vs. saline, p<.05, n=3). These studies demonstrate a key role for ROS in Ang‐II‐dependent CaMKII activation in neurons, and implicate CaMKII as a potential downstream effector of Ang‐II‐induced ROS in the development of neurogenic hypertension.